Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

The purpose of this study is to characterize the effect of Cobicistat based regimens on parameters of renal function in HIV infected patients with mild to moderate renal impairment, and also, to assess the safety and tolerability of those regimens in order to generate appropriate dosing recommendations.

• Acquired Immunodeficiency Syndrome
• HIV Infections

• Drug: elvitegravir/cobicistat/emtricitabine/tenofovir DF
  Cohort 1: Single tablet regimen of elvitegravir 150mg/ cobicistat 150 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg (n = at least 33 subjects)
• Drug: cobicistat and atazanavir or cobicistat and darunavir
  Cohort 2: cobicistat boosted atazanavir + 2 NRTIs or cobicistat boosted darunavir + 2 NRTIs

• Experimental: elvitegravir/cobicistat/emtricitabine/tenofovir DF
  Single tablet regimen (STR) of elvitegravir (EVG) 150mg/ cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg (EVG/COBI/FTC/TDF)
  Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir DF
• Experimental: cobicistat and atazanavir or cobicistat and darunavir
  cobicistat boosted atazanavir + 2 NRTIs OR cobicistat boosted darunavir + 2 NRTIs
  Intervention: Drug: cobicistat and atazanavir or cobicistat and darunavir

Inclusion Criteria:

Cohort 1 (Treatment Naïve)

• Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
• Screening genotype report must show sensitivity to FTC and TDF
• No prior use of any approved or investigational antiretroviral drug for any length of time

Cohort 2 (Pharmacoenhancer Switch)

• Subjects must be receiving ATV 300 mg/RTV 100 mg plus 2 NRTIs OR DRV 800 mg/RTV 100 mg plus 2 NRTIs for at least 6 months prior to screening
• Plasma HIV-1 RNA concentrations at undetectable levels in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
• Subjects experiencing intolerance to RTV (as determined by the Investigator)

Cohort 1 and Cohort 2

• The ability to understand and sign a written informed consent form
• Normal ECG
• Mild to Moderate renal function
• Stable renal function
• Hepatic transaminases (AST and ALT) ≤ 5 x ULN
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert's Syndrome or hyperbilirubinemia due to atazanavir therapy may have total bilirubin up to 5 x upper limit of normal)
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN
• Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
• Age ≥ 18 years

Exclusion Criteria:

• New AIDS defining condition diagnosed within the 30 days prior to screening
• Receiving drug treatment for Hepatitis C, or anticipated to receive treatment for Hepatitis C
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Receiving ongoing therapy with any of medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR, COBI tablets, atazanavir capsules or darunavir tablets or contraindicated for the 2 NRTIs as part of the Cohort 2 regimen
• Participation in any other clinical trial without prior approval
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements